Age-associated dysregulation of microglial activation is coupled with enhanced blood-brain barrier permeability and pathology in APP/PS1 mice

Minogue, Aedín M.; Jones, Raasay S.; Kelly, Ronan J.; McDonald, Claire; Connor, Thomas J.; Lynch, Marina A.

doi:10.1016/j.neurobiolaging.2013.12.026

Cited by 95 publications

(97 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, continued upregulation of these markers have been reported in aged mice of 14 and 24 months old (Minogue et al, 2014). Furthermore, increased expression of proinflammatory cytokines has also been characterised in this model with increased mRNA expression of IL-1␤ and TNF-␣ apparent from eight months old (Hickman et al, 2008) and persisting up to 24 months old (Minogue et al, 2014). Similar evidence of neuroinflammation has been reported in the triple transgenic AD model with increased numbers of resting and activated microglia observed at nine and twelve months old respectively (Rodriguez et al, 2010) and increased mRNA expression of a panel of pro-inflammatory cytokines in 16 month old transgenic mice (Zaheer et al, 2013).…”

Section: Neuroinflammation In Admentioning

confidence: 93%

“…In the APP SWE /PS-1 E9 model, increased mRNA expression of the microglial markers Iba1 and CD68 have been reported in mice as early as three months old (Johansson et al, 2015). Indeed, continued upregulation of these markers have been reported in aged mice of 14 and 24 months old (Minogue et al, 2014). Furthermore, increased expression of proinflammatory cytokines has also been characterised in this model with increased mRNA expression of IL-1␤ and TNF-␣ apparent from eight months old (Hickman et al, 2008) and persisting up to 24 months old (Minogue et al, 2014).…”

Section: Neuroinflammation In Admentioning

confidence: 99%

See 1 more Smart Citation

Exercise as a pro-cognitive, pro-neurogenic and anti-inflammatory intervention in transgenic mouse models of Alzheimer’s disease

Ryan

Kelly

2016

Ageing Research Reviews

View full text Add to dashboard Cite

a b s t r a c tIt is now well established, at least in animal models, that exercise elicits potent pro-cognitive and proneurogenic effects. Alzheimer's disease (AD) is one of the leading causes of dementia and represents one of the greatest burdens on healthcare systems worldwide, with no effective treatment for the disease to date. Exercise presents a promising non-pharmacological option to potentially delay the onset of or slow down the progression of AD. Exercise interventions in mouse models of AD have been explored and have been found to reduce amyloid pathology and improve cognitive function. More recent studies have expanded the research question by investigating potential pro-neurogenic and anti-inflammatory effects of exercise. In this review we summarise studies that have examined exercise-mediated effects on AD pathology, cognitive function, hippocampal neurogenesis and neuroinflammation in transgenic mouse models of AD. Furthermore, we attempt to identify the optimum exercise conditions required to elicit the greatest benefits, taking into account age and pathology of the model, as well as type and duration of exercise.© 2016 Elsevier B.V. All rights reserved. Please cite this article in press as: Ryan, S.M., Kelly, Á.M., Exercise as a pro-cognitive, pro-neurogenic and anti-inflammatory intervention in transgenic mouse models of Alzheimer's disease. Ageing Res. Rev. (2016), http://dx

show abstract

Section: Neuroinflammation In Admentioning

confidence: 93%

Section: Neuroinflammation In Admentioning

confidence: 99%

Exercise as a pro-cognitive, pro-neurogenic and anti-inflammatory intervention in transgenic mouse models of Alzheimer’s disease

Ryan

Kelly

2016

Ageing Research Reviews

View full text Add to dashboard Cite

show abstract

“…Mice received intraperitoneal injections of sterile PBS (control) or MCC950 (10 mg/kg in PBS) every second day for 3 months and in the 8th and 9th week of treatment, their performance in a T-maze and a novel object recognition task was assessed. At the end of the 3-month treatment, mice were anaesthetized, transcardially perfused and the brain was removed (Minogue et al, 2014). One half was stored for later preparation of sections for immunohistochemistry, and the hippocampus and cortex were dissected free from the other side of the brain and flash frozen for later analysis.…”

Section: Treatment Schedulementioning

confidence: 99%

Inhibiting the NLRP3 inflammasome with MCC950 promotes non-phlogistic clearance of amyloid-β and cognitive function in APP/PS1 mice

Dempsey

Rubio-Araiz

Bryson

et al. 2017

Brain, Behavior, and Immunity

412

284

View full text Add to dashboard Cite

., Inhibiting the NLRP3 inflammasome with MCC950 promotes non-phlogistic clearance of amyloid-β and cognitive function in APP/PS1 mice, Brain, Behavior, and Immunity (2016), doi: http://dx.doi.org/10. 1016/j.bbi.2016.12.014 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Inhibiting the NLRP3 inflammasome with MCC950 promotes non-phlogistic clearance of amyloid-β and cognitive function in APP/PS1 mice Activation of the inflammasome is implicated in the pathogenesis of an increasing number of inflammatory diseases, including Alzheimer's disease (AD). Research reporting inflammatory changes in post mortem brain tissue of individuals with AD and GWAS data have convincingly demonstrated that neuroinflammation is likely to be a key driver of the disease. This, together with the evidence that genetic variants in the NLRP3 gene impacts on the risk of developing late-onset AD, indicates that targetting inflammation offers a therapeutic opportunity. Here, we examined the effect of the small molecule inhibitor of the NLRP3 inflammasome, MCC950, on microglia in vitro and in vivo. The findings indicate that MCC950 inhibited LPS+Aβ-induced caspase 1 activation in microglia and this was accompanied by IL-1β release, without inducing pyroptosis. We demonstrate that MCC950 also inhibited inflammasome activation and microglial activation in the APP/PS1 mouse model of AD. Furthermore, MCC950 stimulated Aβ phagocytosis in vitro, and it reduced Aβ accumulation in APP/PS1 mice, which was associated with improved cognitive function. These data suggest that activation of the inflammasome contributes to amyloid accumulation and to the deterioration of neuronal function in APP/PS1 mice and demonstrate that blocking assembly of the inflammasome may prove to be a valuable strategy for attenuating changes that negatively impact on neuronal function.

show abstract

“…[40] Being atherosclerosis and cerebrovascular disease common in older HIV-positive patients this may be relevant. Meningeal inflammation (usually observed in acute infection, rebound encephalitis, CSF escape or with opportunistic infections) has the potential to modulate the penetration of ARVs: this is mediated by blood flow, BBB impairment and pH modifications.…”

Section: Patients' Characteristics and Blood Brain Barrier Damagementioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of Antiretrovirals in the Central Nervous System

2014

View full text Add to dashboard Cite

show abstract

Age-associated dysregulation of microglial activation is coupled with enhanced blood-brain barrier permeability and pathology in APP/PS1 mice

Cited by 95 publications

References 61 publications

Exercise as a pro-cognitive, pro-neurogenic and anti-inflammatory intervention in transgenic mouse models of Alzheimer’s disease

Exercise as a pro-cognitive, pro-neurogenic and anti-inflammatory intervention in transgenic mouse models of Alzheimer’s disease

Inhibiting the NLRP3 inflammasome with MCC950 promotes non-phlogistic clearance of amyloid-β and cognitive function in APP/PS1 mice

Pharmacokinetics and Pharmacodynamics of Antiretrovirals in the Central Nervous System

Contact Info

Product

Resources

About